RRC ID 56187
著者 Laurent P, Ch'ng Q, Jospin M, Chen C, Lorenzo R, de Bono M.
タイトル Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron.
ジャーナル Proc Natl Acad Sci U S A
Abstract Neuropeptides are ubiquitous modulators of behavior and physiology. They are packaged in specialized secretory organelles called dense core vesicles (DCVs) that are released upon neural stimulation. Unlike synaptic vesicles, which can be recycled and refilled close to release sites, DCVs must be replenished by de novo synthesis in the cell body. Here, we dissect DCV cell biology in vivo in a Caenorhabditis elegans sensory neuron whose tonic activity we can control using a natural stimulus. We express fluorescently tagged neuropeptides in the neuron and define parameters that describe their subcellular distribution. We measure these parameters at high and low neural activity in 187 mutants defective in proteins implicated in membrane traffic, neuroendocrine secretion, and neuronal or synaptic activity. Using unsupervised hierarchical clustering methods, we analyze these data and identify 62 groups of genes with similar mutant phenotypes. We explore the function of a subset of these groups. We recapitulate many previous findings, validating our paradigm. We uncover a large battery of proteins involved in recycling DCV membrane proteins, something hitherto poorly explored. We show that the unfolded protein response promotes DCV production, which may contribute to intertissue communication of stress. We also find evidence that different mechanisms of priming and exocytosis may operate at high and low neural activity. Our work provides a defined framework to study DCV biology at different neural activity levels.
巻・号 115(29)
ページ E6890-E6899
公開日 2018-7-17
DOI 10.1073/pnas.1714610115
PII 1714610115
PMID 29959203
PMC PMC6055185
MeSH Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Mutation* Neuropeptides* / genetics Neuropeptides* / metabolism Secretory Vesicles* / genetics Secretory Vesicles* / metabolism Sensory Receptor Cells / metabolism* Synaptic Vesicles* / genetics Synaptic Vesicles* / metabolism
IF 9.58
引用数 1
リソース情報
線虫 tm4076 tm745 tm1898 tm5776 tm2426 tm3786 tm3697 tm1871 tm1330 tm4773 tm2526